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单胺神经递质转运体的细胞和分子层面

Cellular and molecular aspects of monoamine neurotransmitter transporters.

作者信息

Kitayama S, Dohi T

机构信息

Department of Pharmacology, Hiroshima University School of Dentistry, Japan.

出版信息

Jpn J Pharmacol. 1996 Nov;72(3):195-208. doi: 10.1254/jjp.72.195.

Abstract

Neurotransmitter transporters terminate synaptic neurotransmission by accumulating neurotransmitters once again after release in a sodium- and chloride-dependent fashion. The availability of the cloned neurotransmitter transporters has allowed investigation into the roles of these transporters in neuronal function. Molecular biological and protein engineering studies including in vitro site-directed mutagenesis, chimera formation of several transporter clones, or epitope-tagging various regions of transporter proteins, have revealed the topology and functionally mapped the transporter proteins. Monoamine neurotransmitter transporters such as those for dopamine, norepinephrine and serotonin are of interest, since they are a target of drugs of abuse and are involved in neuronal disorders including Parkinson's disease and depression. Therefore, elucidating the molecular basis of these transporters may clarify these problems and help develop treatments with which to combat these disorders and drug abuse.

摘要

神经递质转运体通过在释放后以依赖钠和氯的方式再次积累神经递质来终止突触神经传递。克隆的神经递质转运体的可得性使得人们能够研究这些转运体在神经元功能中的作用。包括体外定点诱变、几个转运体克隆的嵌合体形成或转运体蛋白各个区域的表位标记在内的分子生物学和蛋白质工程研究,已经揭示了转运体蛋白的拓扑结构并对其进行了功能定位。诸如多巴胺、去甲肾上腺素和5-羟色胺等单胺神经递质转运体备受关注,因为它们是滥用药物的靶点,并且与包括帕金森病和抑郁症在内的神经元疾病有关。因此,阐明这些转运体的分子基础可能会澄清这些问题,并有助于开发对抗这些疾病和药物滥用的治疗方法。

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